Adolescents diagnosed with fragile X syndrome (FXS), the leading known cause of inherited intellectual disability, commonly engage in severe disruptive behaviors (i.e., self-injury and aggression) that can significantly impact the individua's educational progress and functioning. However, the biological and behavioral mechanisms underlying these pathological behaviors are very poorly understood. In this proposal, we aim to examine the extent to which autonomic nervous system arousal interacts with environmental factors (positive and negative reinforcement processes) to exacerbate and maintain self-injury/aggression in FXS. Screening of potential participants will be conducted using the Functional Analysis Screening Tool(c) which will allow us establish the prevalence, frequency, severity, and circumstances surrounding the occurrence of self- injury/aggression in FXS. We will also screen individuals with intellectual disability (ID) who do not have FXS. From the screening, 30 individuals with FXS and 30 ID controls will be selected to travel to Stanford University for a 3-day assessment of their self-injury/aggression. These participants will be aged 11 to 18 years and engage in self-injury/aggression with moderate to severe intensity on a daily basis. Participants with FXS will be matched to ID control participants with respect to age, functioning level, and degree of autistic symptom severity. This comparison group will allow us to determine whether the behavioral characteristics of FXS are specific to FXS, or characteristic of individuals with ID in general. Each subject will undergo a Functional Analysis, conducted by a Board Certified Behavior Analyst, to identify the environmental factors maintaining the child's self-injury/aggression. The Functional Analysis will include both standard and FXS-specific conditions (e.g. transitions and social demands). To examine the influence of physiological factors, we will measure physiological responses and salivary cortisol levels both at Baseline and during the Functional Analysis. The results of this project will directly help individuals with FXS and their families, as well as greatly advance the understanding of self-injury/aggression in FXS, providing sorely needed empirical data to inform interventions in the future for both FXS and other individuals with ID. The project will also significantly improve our understanding of the complex interplay between physiological and environmental factors in co-morbid behaviors in individuals with FXS.